Bone Marrow Liver Thymic mice (BLT mice) have been shown to develop a human immune system with high human T cell and other cell counts in virtually all of their tissues, including the gut and lungs, sites of important immune response to diseases (Melkus, et al. (2006) Nat. Med. 12:1316-22). BLT mice are produced by non-lethally irradiating non-obese diabeticsevere combined immunodeficient crossed mice (nodscid and nodSCIDγc−/−) at 6 weeks with 2 γG of radiation (Brainard, et al. (2009) J. Virology 83:7305-7321). These irradiated mice pups have human fetal liver surgically implanted under the kidney capsule of both kidneys in association with the IV injection of CD34+ cells from human fetal liver. These mice have high levels of human CD45+ blood cells by 12 weeks after the transplant, wherein the CD45+ cells generally encompass roughly equal levels of B cells and T cells.
It is has been shown that the antigen-specific T cell response cannot be elicited in mice transplanted with only CD34+ haematopoietic stem cells because the T cells fail to develop normally in such mice (Sato, et al. (2010) PLoS One 5:e13109). Additionally, antigen-specific IgG+ human B cell clones have not been established in these animals because T cell help in this system is sub-optimal resulting in an absence of an antigen-specific T cell response (Becker, et al. (2010) PLoS One 5(10):e13137). A low frequency of IgG+ producing cells has been noted; however, it was concluded that antigen-specific IgG antibodies cannot be obtained with this model. Rather, antigen-specific human monoclonal IgM antibodies were produced.